TY - JOUR T1 - Genetics of Psoriasis and Psoriatic Arthritis: A Report from the GRAPPA 2010 Annual Meeting JF - The Journal of Rheumatology JO - J Rheumatol SP - 431 LP - 433 DO - 10.3899/jrheum.111242 VL - 39 IS - 2 AU - PROTON RAHMAN AU - JAMES T. ELDER Y1 - 2012/02/01 UR - http://www.jrheum.org/content/39/2/431.abstract N2 - Psoriasis vulgaris (PsV) and psoriatic arthritis (PsA) are interrelated disorders, PsA representing a disease within a disease. From an epidemiological perspective, the genetic contributions of PsV and PsA are now well documented. HLA-C is firmly established as a PsV/PsA gene, with HLA-Cw*0602 as a major risk allele. Fine-mapping studies within the MHC region in PsV and PsA have identified novel loci that are independent of the HLA-Cw6 allele. Recent genome-wide association scans have led to a substantial increase in the number of candidate genes reaching genome-wide significance in PsV and PsA cohorts. Most of these genes can be grouped into an integrated pathogenic model of PsV/psoriatic disease comprising distinct signaling networks affecting skin barrier function (LCE3, DEFB4, GJB2), innate immune responses involving nuclear factor-κB and interferon signaling (TNFAIP3, TNIP1, NFKBIA, REL, FBXL19, TYK2, NOS2), and adaptive immune responses involving CD8 T lymphocytes and interleukin 23 (IL-23)/IL-17-mediated lymphocyte signaling (HLA-C, IL12B, IL23R, IL23A, TRAF3IP2, ERAP1). Further development of a global genetic risk score and inclusion of potential gene/gene and gene/environment interactions will likely enhance the predictive value of recently identified genetic variants. ER -